Conventionally, almost all components effective for promotion or suppression of restoration or development of hairs on the head or body have been obtained by screening synthetic compounds or natural substances in plants or microorganisms for those having such activity in e.g. experimental animals. However, because the trophic environments of hair roots were believed to be essential, conventional developments in hair restoration promoting agents, hair restoration suppressing agents and hair developing agents were based on improvement or suppression of topical blood circulation or environmental conditions for hair roots, but not on the mechanism of production of animal hairs.
Fibroblast growth factor-5 (FGF-5) is known to have growth promoting activity and transforming activity on fibroblasts as its physiological functions. If NIH3T3 fibroblasts are transformed with an FGF-5 gene under the control of a constant-expression vector, their growth ability is known to be altered by FGF-5. Also, FGF-5 secreted from these transformed cells into the culture significantly promotes the proliferation ability of other fibroblast BALB/c3T 3 cells. Further, an FGF-5 polypeptide expressed by E. coli transformed with an FGF-5 gene expression plasmid significantly promotes the proliferation ability of BALB/c3T3 as well.
The activity of FGF-5 as a neurotrophic factor is also known and expressed in skeletal muscle cells. Both FGF-5 contained in an extract of these skeletal muscle cells and FGF-5 expressed in the E. coli transformed with the FGF-5 gene expression plasmid are known to significantly promote the survival of cultured motor neurons. This fact strongly suggests that FGF-5 is a trophic factor of motor neurons. The expression of FGF-5 in mouse and rat brains was further found and it is believed from an experiment with brain nerve primary culture cells that FGF-5 acts as a trophic factor of cholinergic and serotonergic neurons in the brain.
The activity of FGF-5 as a neurotrophic factor came to be known as described above, and much attention is paid to a regulatory factor for the activity, but none of such regulatory factor has been found.
In the generation of the FGF-5 protein, it is known that a gene coding for the FGF-5 protein is transcribed into mRNA which in turn undergoes splicing such that exon 1, exon 2 and exon 3 are linked in this order to form a continuous chain in mature RNA. That is, its translational frame begins at the translational initiation codon ATG (coding for methionine) in exon 1, proceeds through exon 2 and ends at a termination codon in exon 3 to result in a protein composed of 268 amino acids in human or a protein of 264 amino acids in mouse (Zhan, X. et al., Mol. Cell. Biol., Vol. 8, pp. 3487-3495 (1988); Haub. O. et al., Proc. Natl. Acad. Sci., USA, Vol. 87, pp. 8022-8026 (1990)).